It was first thought that the E3 ligase activity may play an important role in DNA repair and/or tumor suppression; however, mouse cells carrying a I26A knockin allele did not show any significant defect in HR activity (Reid et al., 2008), and the mutant protein was still able to suppress mammary tumor development in Brca1 conditional knockout models (Shakya et al., 2011). This evidence concerns the gene BRCA1 and breast cancer.